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ANESTHETIC PHARMACOLOGY

The Effects of Anesthetics and Ethanol on ₂ Adrenoceptor Subtypes Expressed with G Protein-Coupled Inwardly Rectifying Potassium Channels in Xenopus Oocytes

Koji Hara, MD, PhD^*, Tomohiro Yamakura, MD, PhD, Takeyoshi Sata, MD, PhD, and R. Adron Harris, PhD^*

*Waggoner Center for Alcohol and Addiction Research and Institute for Cellular and Molecular Biology, University of Texas at Austin; Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu; and Division of Anesthesiology, Niigata University Graduate School of Medical and Dental Sciences, Japan

Address correspondence and reprint requests to Koji Hara, MD, PhD, Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu, 807-8555, Japan. Address e-mail to kojihara{at}med.uoeh-u.ac.jp.

A wide range of physiological effects are mediated by ₂-adrenoceptors (ARs) through their association with G protein-coupled inwardly rectifying potassium (GIRK) channels. Although ₂-ARs are divided into three subtypes (_2A–C), a pharmacological distinction among the subtypes is difficult to establish because of the lack of a selective agonist and antagonist; therefore, little is known about the effects of anesthetics on the ₂-AR subtypes. We expressed each subtype together with GIRK1/GIRK2 subunits in Xenopus oocytes and observed ₂-AR-mediated GIRK1/GIRK2 currents to test the effects of ethanol, halothane, and several IV anesthetics at clinical concentrations. UK 14,304, a selective ₂-AR agonist, evoked GIRK1/GIRK2 currents in every subtype. None of the IV anesthetics, which included pentobarbital, propofol, ketamine, and alphaxalone, influenced UK 14,304-evoked potassium currents in any of the receptor subtypes. Ethanol enhanced the UK 14,304-evoked potassium currents, whereas halothane inhibited the currents. However, these effects were not significantly different from those on the baseline-GIRK1/GIRK2 current, suggesting that neither ethanol nor halothane acts directly on the ₂-AR subtypes. Although none of the drugs examined had any effect on the ₂-ARs, the physiological actions of the ₂-ARs mediated by the GIRK1/GIRK2 channels may be affected by ethanol and halothane.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999